2-218675520-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTTT

Variant names:

• chr2-218675520-C-CTT
• rs33970984
• NM_015690.5:c.434+67_434+68dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015690.5(STK36):​c.434+67_434+68dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,141,238 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0046 (2 hom.)
• Consequence: STK36 NM_015690.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 1 publications found

Genes affected

STK36 (HGNC:17209): (serine/threonine kinase 36) This gene encodes a member of the serine/threonine kinase family of enzymes. This family member is similar to a Drosophila protein that plays a key role in the Hedgehog signaling pathway. This human protein is a positive regulator of the GLI zinc-finger transcription factors. Knockout studies of the homologous mouse gene suggest that defects in this human gene may lead to congenital hydrocephalus, possibly due to a functional defect in motile cilia. Because Hedgehog signaling is frequently activated in certain kinds of gastrointestinal cancers, it has been suggested that this gene is a target for the treatment of these cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

STK36 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 46

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015690.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK36	NM_015690.5	MANE Select	c.434+67_434+68dupTT		intron	N/A	NP_056505.2	Q9NRP7-1
	STK36	NM_001369423.1		c.434+67_434+68dupTT		intron	N/A	NP_001356352.1	Q9NRP7-1
	STK36	NM_001243313.2		c.434+67_434+68dupTT		intron	N/A	NP_001230242.1	Q9NRP7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK36	ENST00000295709.8	TSL:1 MANE Select	c.434+47_434+48insTT		intron	N/A	ENSP00000295709.3	Q9NRP7-1
	STK36	ENST00000392105.7	TSL:1	c.434+47_434+48insTT		intron	N/A	ENSP00000375954.3	Q9NRP7-2
	STK36	ENST00000440309.5	TSL:5	c.434+47_434+48insTT		intron	N/A	ENSP00000394095.1	Q9NRP7-1

Frequencies

GnomAD3 genomes AF: 0.000889 AC: 102 AN: 114774 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000349

Gnomad AMI AF: 0.00402

Gnomad AMR AF: 0.000439

Gnomad ASJ AF: 0.000341

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00112

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00664 AC: 394 AN: 59338 AF XY: 0.00608

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.00744

Gnomad ASJ exome AF: 0.00619

Gnomad EAS exome AF: 0.0104

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.00691

Gnomad OTH exome AF: 0.00917

GnomAD4 exome AF: 0.00461 AC: 4731 AN: 1026462 Hom.: 2 Cov.: 0 AF XY: 0.00465 AC XY: 2367 AN XY: 508790

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00232 AC: 50 AN: 21536

American (AMR) AF: 0.00453 AC: 91 AN: 20102

Ashkenazi Jewish (ASJ) AF: 0.00542 AC: 80 AN: 14756

East Asian (EAS) AF: 0.00457 AC: 114 AN: 24954

South Asian (SAS) AF: 0.00760 AC: 432 AN: 56870

European-Finnish (FIN) AF: 0.00621 AC: 149 AN: 24004

Middle Eastern (MID) AF: 0.00298 AC: 8 AN: 2682

European-Non Finnish (NFE) AF: 0.00435 AC: 3567 AN: 820866

Other (OTH) AF: 0.00590 AC: 240 AN: 40692

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000889 AC: 102 AN: 114776 Hom.: 0 Cov.: 27 AF XY: 0.000932 AC XY: 51 AN XY: 54720

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000349 AC: 10 AN: 28692

American (AMR) AF: 0.000438 AC: 5 AN: 11404

Ashkenazi Jewish (ASJ) AF: 0.000341 AC: 1 AN: 2936

East Asian (EAS) AF: 0.00101 AC: 4 AN: 3954

South Asian (SAS) AF: 0.00112 AC: 4 AN: 3570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.00134 AC: 75 AN: 55850

Other (OTH) AF: 0.00 AC: 0 AN: 1596

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00255 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.010

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs33970984; hg19: chr2-219540243;